ClinVar Genomic variation as it relates to human health
NM_018344.6(SLC29A3):c.300+1G>A
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_018344.6(SLC29A3):c.300+1G>A
Variation ID: 130339 Accession: VCV000130339.20
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 10q22.1 10: 71323055 (GRCh38) [ NCBI UCSC ] 10: 73082812 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Apr 4, 2013 Feb 14, 2024 May 16, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_018344.6:c.300+1G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
splice donor NM_001174098.2:c.300+1G>A splice donor NM_001363518.2:c.66+1G>A splice donor NC_000010.11:g.71323055G>A NC_000010.10:g.73082812G>A NG_017066.2:g.8797G>A LRG_1318:g.8797G>A LRG_1318t1:c.300+1G>A - Protein change
- Other names
- IVS2, G-A, +1
- Canonical SPDI
- NC_000010.11:71323054:G:A
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD) 0.00001
Trans-Omics for Precision Medicine (TOPMed) 0.00002
The Genome Aggregation Database (gnomAD), exomes 0.00006
Exome Aggregation Consortium (ExAC) 0.00007
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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SLC29A3 | - | - |
GRCh38 GRCh37 |
479 | 508 |
Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Pathogenic (4) |
criteria provided, multiple submitters, no conflicts
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May 16, 2023 | RCV000118377.13 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
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The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
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This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Pathogenic
(Feb 03, 2014)
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criteria provided, single submitter
Method: clinical testing
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Histiocytosis-lymphadenopathy plus syndrome
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
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Genetic Services Laboratory, University of Chicago
Accession: SCV000152777.1
First in ClinVar: May 17, 2014 Last updated: May 17, 2014 |
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Pathogenic
(Jan 03, 2022)
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criteria provided, single submitter
Method: clinical testing
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H syndrome
Affected status: yes
Allele origin:
germline
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3billion
Accession: SCV002058999.1
First in ClinVar: Jan 15, 2022 Last updated: Jan 15, 2022 |
Comment:
Canonical splice site: predicted to alter splicing and result in a loss or disruption of normal protein function through protein truncation. Multiple pathogenic variants are … (more)
Canonical splice site: predicted to alter splicing and result in a loss or disruption of normal protein function through protein truncation. Multiple pathogenic variants are reported in the predicted truncated region (PVS1_VS).The variant has been reported at least twice as pathogenic/likely pathogenic with clinical assertions and evidence for the classification (ClinVar ID: VCV000130339).It is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.000064, PM2_M). Each parent is heterozygous for the variant (PM3_P, 3billion dataset). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline. (less)
Clinical Features:
Anemia (present) , Sensorineural hearing loss disorder (present) , Diabetes mellitus (present) , Increased circulating antibody concentration (present) , Short stature (present) , Proportionate short … (more)
Anemia (present) , Sensorineural hearing loss disorder (present) , Diabetes mellitus (present) , Increased circulating antibody concentration (present) , Short stature (present) , Proportionate short stature (present) , Thrombocytosis (present) , Diabetes mellitus type 1 (present) , Ascites (present) , Pericardial effusion (present) , Pleural effusion (present) , Severe sensorineural hearing impairment (present) , Thrombocytosis (present) (less)
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Pathogenic
(May 16, 2023)
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criteria provided, single submitter
Method: clinical testing
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H syndrome
Affected status: unknown
Allele origin:
germline
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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV002234641.3
First in ClinVar: Mar 28, 2022 Last updated: Feb 14, 2024 |
Comment:
This variant is present in population databases (rs587780463, gnomAD 0.03%). This sequence change affects a donor splice site in intron 2 of the SLC29A3 gene. … (more)
This variant is present in population databases (rs587780463, gnomAD 0.03%). This sequence change affects a donor splice site in intron 2 of the SLC29A3 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in SLC29A3 are known to be pathogenic (PMID: 19336477, 20595384, 23406517, 25963354). For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 130339). Disruption of this splice site has been observed in individuals with SLC29A3-related conditions (PMID: 20140240, 27215564). (less)
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Pathogenic
(Feb 05, 2010)
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no assertion criteria provided
Method: literature only
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HISTIOCYTOSIS-LYMPHADENOPATHY PLUS SYNDROME
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000045227.1
First in ClinVar: Apr 04, 2013 Last updated: Apr 04, 2013 |
Comment on evidence:
In 2 Pakistani brothers diagnosed with Faisalabad histiocytosis (602782), originally reported by Moynihan et al. (1998), Morgan et al. (2010) identified homozygosity for a +1G-A … (more)
In 2 Pakistani brothers diagnosed with Faisalabad histiocytosis (602782), originally reported by Moynihan et al. (1998), Morgan et al. (2010) identified homozygosity for a +1G-A transition in intron 2 of the SLC29A3 gene. The mutation segregated with disease in the family and was not found in 384 ethnically matched control chromosomes. RT-PCR analysis of lymphocyte RNA from a heterozygous family member revealed monoallelic expression of an exon 2 coding region SNP without detection of any abnormally sized transcripts, consistent with nonsense mediated RNA decay. (less)
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Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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A Case of SLC29A3 Spectrum Disorder-Unresponsive to Multiple Immunomodulatory Therapies. | Mistry A | Journal of clinical immunology | 2016 | PMID: 27215564 |
Identification of a novel mutation in solute carrier family 29, member 3 in a Chinese patient with H syndrome. | Liu JW | Chinese medical journal | 2015 | PMID: 25963354 |
Agenesis of the inferior vena cava in H syndrome due to a novel SLC29A3 mutation. | Mutlu GY | Pediatric dermatology | 2013 | PMID: 23406517 |
Human equilibrative nucleoside transporter-3 (hENT3) spectrum disorder mutations impair nucleoside transport, protein localization, and stability. | Kang N | The Journal of biological chemistry | 2010 | PMID: 20595384 |
Mutations in SLC29A3, encoding an equilibrative nucleoside transporter ENT3, cause a familial histiocytosis syndrome (Faisalabad histiocytosis) and familial Rosai-Dorfman disease. | Morgan NV | PLoS genetics | 2010 | PMID: 20140240 |
SLC29A3 gene is mutated in pigmented hypertrichosis with insulin-dependent diabetes mellitus syndrome and interacts with the insulin signaling pathway. | Cliffe ST | Human molecular genetics | 2009 | PMID: 19336477 |
Splicing in action: assessing disease causing sequence changes. | Baralle D | Journal of medical genetics | 2005 | PMID: 16199547 |
Autozygosity mapping, to chromosome 11q25, of a rare autosomal recessive syndrome causing histiocytosis, joint contractures, and sensorineural deafness. | Moynihan LM | American journal of human genetics | 1998 | PMID: 9545394 |
Text-mined citations for rs587780463 ...
HelpRecord last updated Sep 29, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.